Promising new treatments for drug-resistant tuberculosis Study confirms safety and efficacy of two new drugs

Two recent international studies have yielded promising results for the treatment of drug-resistant tuberculosis. In these studies, researchers from PANACEA, an international consortium led by Radboud university medical center in close collaboration with the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich, investigated the effectiveness and safety of the drugs sutezolid and delpazolid as alternatives to linezolid—a commonly used medication known for its many side effects. The positive results of these studies have now been published in The Lancet Infectious Diseases.

World’s deadliest infectious disease

Tuberculosis (TB) is a bacterial infectious disease that affects 9 million people annually worldwide, primarily in low-income countries. It is the deadliest infectious disease globally, causing nearly 1.3 million deaths in 2023. The disease is treatable but requires a relatively long six-month course of antibiotics consisting of a combination of four drugs. In cases of drug-resistant TB, where standard treatment fails, the treatment duration can extend up to 1.5 years.

At Radboudumc, a team of TB researchers - including among others Jodie Schildkraut, Lindsey te Brake, Elin Svensson, and Rob Aarnoutse - have been working within the PanACEA consortium for the past fifteen years to improve and optimize existing treatments. The researchers also aimed to shorten treatment durations, especially for drug-resistant TB. Jodie Schildkraut, coordinator of the PanACEA consortium at Radboudumc, explains: ‘In some African countries where TB is prevalent, healthcare is not always easily accessible. Many people struggle to complete long treatment regimens. That’s why we explored ways to improve this within PanACEA.’

One of the drugs used for drug-resistant TB is linezolid. While effective, it causes so many side effects that many patients are forced to discontinue it. Schildkraut notes: ‘These include neurological issues, such as loss of sensation in hands and feet.’ This prompted the search for a suitable alternative.

Two drugs show promise

The results of two studies have now been published in The Lancet Infectious Diseases. In the first study, 76 participants from Tanzania and South Africa received various doses of delpazolid. A 1200 mg once-daily dose proved safe and effective, with minimal side effects. This makes delpazolid a promising replacement for linezolid in TB treatment, potentially with fewer side effects.

In the second study, researchers examined sutezolid in 75 participants, also from Tanzania and South Africa. Sutezolid was combined with three other drugs. The results showed that sutezolid enhanced treatment efficacy without causing severe nerve damage. Some side effects were observed, such as liver issues and changes in heart rhythm, but these were significantly fewer than those with linezolid. According to the researchers, this makes sutezolid a promising and safer alternative, although the optimal dosage still needs further investigation.

These so-called phase 2b studies focused on the efficacy and safety of both drugs. Follow-up studies are needed to confirm optimal dosages and evaluate long-term safety and effectiveness. But the results are encouraging, says lead researcher Elin Svensson, who led both studies. ‘These findings show there is hope for better drugs for drug-resistant TB. Without the collaboration within PanACEA, this would not have been possible in such a short time. It highlights the importance of tackling TB as a global community.’

About the publications

The DECODE study is published in The Lancet Infectious Diseases: A prospective, randomised, open label phase 2b dose-finding trial of delpazolid in combination with bedaquiline, delamanid and moxifloxacin for pulmonary tuberculosis: DECODE. Lilian Tina Minja, Isabella van der Feltz, Christina Manyama [...], Derek Sloan, Lindsey te Brake, Jodie Schildkraut, Rob Aarnoutse, Timothy McHugh, Leticia Wildner, Martin Boeree, Lawrence Geiter, Young-Lag Cho, Brian Aldana, Patrick Phillips, Michael Hoelscher, Elin Svensson, Norbert Heinrich, on behalf of the PanACEA consortium. DOI: 10.1016/S1473-3099(25)00289-0.

The SUDOCU study is published in The Lancet Infectious Diseases: A prospective, randomised, open label phase 2b dose-finding trial of sutezolid in combination with bedaquiline, delamanid and moxifloxacin for pulmonary tuberculosis: SUDOCU. Norbert Heinrich, Christina Manyama, Simon Koele, [...], Derek Sloan, Lindsey te Brake, Jodie Schildkraut, Rob Aarnoutse, Timothy McHugh, Leticia Wildner, Martin Boeree, Brian Aldana, Patrick Phillips, Michael Hoelscher, Elin Svensson, on behalf of the PanACEA consortium. DOI: 10.1016/S1473-3099(25)00213-0.

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